The major strength of the Utah site of the Breast Cancer Family Registry (B-CFR) is the cost-effective enrollment of multiple members of families who are at the highest risk for breast cancer because they have mutations in breast cancer predisposition genes. In addition, we have close and regular clinical contact with members of these families through provision of clinical oncology and genetic counseling services by key personnel of the Utah B-CFR. Each of the major research themes of the restructured B-CFR genetic factors associated with breast cancer risk, environmental modifiers of risk, translational and clinical studies, and behavioral response to familial breast cancer will either be enhanced by the enrollment of additional mutation carriers or will be possible primarily because of the therapeutic relationship between the investigators and subjects who will be willing to enroll in studies of screening, prevention, treatment and behavioral/psychosocial issues. In the past 10 years Utah has enrolled about 4 percent of the total subjects accrued to the B-CFR. At the same time, Utah has contributed nearly 24 percent of the total number of the BRCA1 and BRCA2 mutation carriers, most of whom have mutations other than those seen in the Ashkenazi population. Fifty percent of our subjects enrolled in the past 5 years have been mutation carriers. We propose to continue to enroll and collect data and biospecimens from additional subjects and families with germline mutations in BRCA1 and BRCA2. We will also provide leadership for the Clinical/Translational Working Group to identify studies that will assist our understanding of 1) the screening methods that best recognize cancer in BRCA1 or BRCA2 mutation carriers and other high-risk subjects, and 2) the outcomes associated with various treatments and preventive methods. These activities will facilitate the translation of genetic epidemiology into improved medical care for B-CFR participants and breast cancer patients in general.